Cocaine DependencePhase 2Keppra-DBNCT00577005
Efficacy of Levetiracetam in Cocaine-Abusing Methadone Maintained Patients
A Phase 2 study testing levetiracetam in people with Cocaine Dependence and Opioid Dependency, run by Yale University at 1 site in United States.
Trial summary
Concurrent dependence on cocaine occurs in up to 50% of the over one million opiate dependent patients in spite of methadone maintenance treatment being highly effective for opiate dependence and having excellent treatment retention. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Cocaine Dependence, Opioid Dependency
- What is being tested?
- levetiracetam
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 28 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2007to Oct 2008
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Between the ages of 18-65 years.
- Participants must demonstrate current opioid dependence as determined by study physician or APRN, self-reported history of opioid dependence for one year and a positive urine of opiates. Participants may be transferred from other methadone maintenance programs, including the WHVA methadone program.
- Participants also must be current users of cocaine with self-reported use of cocaine > 1 time/week in at least one month preceding study entry, cocaine-positive urine screen and score over 3 as assessed with the Severity Dependence Scale.
- Women of childbearing age are eligible to be included in the study if they have a negative pregnancy test at screening, agree to adequate contraception to prevent pregnancy, to have monthly pregnancy tests, and they understand the risk of fetal toxicity due to medication and cocaine.
Who cannot join
- Current diagnosis of other drug or alcohol dependence (other than opiates, cocaine or tobacco).
- Patients with serious medical illness (e.g., major cardiovascular, renal, endocrine, hepatic, and serious neurological disorders including any history of seizures).
- Patients with current serious psychiatric illness or history of psychosis, schizophrenia, bipolar type I disorder and subjects with suicidal or homicidal thoughts or taking psychotropic medications.
- Women who are pregnant, nursing or refuse to use a reliable form of birth control or refuse monthly testing.
- Screening liver function tests (SGOT or SGPT) greater than 3 times normal and renal function test (creatinine) greater than 1.5 mg/dl.
Trial locations and contacts
1 site in 1 country.
United States1 site
VA CT Healthcare System
West Haven, Connecticut, 06516
About this study
Official title: Levetiracetam (Keppra) Treatment for Cocaine Dependence in Methadone-Maintained Patients
Concurrent dependence on cocaine occurs in up to 50% of the over one million opiate dependent patients in spite of methadone maintenance treatment being highly effective for opiate dependence and having excellent treatment retention. Cocaine dependence has remained largely unresponsive to medications both in and outside of these methadone programs. We have initial data from our open-label study with levetiracetam showing that this medication is well tolerated and may reduce cocaine use in this cocaine-abusing methadone treated population.
The specific aim of this study is to evaluate the efficacy of levetiracetam 3 grams/day in modifying cocaine-using behavior, reducing cocaine craving and attenuating cocaine's reinforcing effect among methadone-maintained patients. The primary outcomes will be reduction in cocaine use as assessed by self-report and thrice-weekly urinalyses. Secondary outcomes will include weeks in treatment (retention) and change in measures of cocaine craving, anxiety symptoms and opiate withdrawal symptoms.
Read the detailed description
This 17-week double-blind, placebo controlled randomized pilot clinical trial will provide treatment for 40 cocaine-dependent opioid dependent patients. Participants, aged 18-65 years, will be randomized to receive levetiracetam 3000 mg/day or placebo while concurrently receiving treatment with methadone. Baseline cocaine use will be determined during the first week of treatment participation. (Gossop et al., 1997) The study design will have three overlapping phases that are summarized below: 1) A one week methadone fixed induction (week 1) and flexible methadone stabilization phase (weeks 2-13); 2) an 12-week "treatment" phase (weeks 2-13), consisting of slow titration and stabilization on study medication; and 3) a four week "taper, detoxification or transfer" phase (weeks 13-17).
During the first week of induction onto methadone, participants will be administered increasing doses of methadone starting at 30 mg daily and increased up to 60 mg daily by the end of the first week. This methadone dose will be adjusted for stabilization of opiate withdrawal symptoms using a flexible dosing from 40 mg up to 150 mg between weeks 2 to 12. This range has been found to be adequate for the vast majority of patients receiving methadone in our program and is designed to accommodate participants who may not be able to tolerate the higher maintenance doses or may still experience withdrawal symptoms, respectively. We may increase or decrease this amount on a case-by-case basis based on physician assessment of self-reported and observed symptoms.
Starting on week 2 subjects will start study medication in one of two randomly assigned experimental groups: levetiracetam 3000 mg /day (active medication) or placebo (inactive medication). Concurrent with the stabilization on methadone, levetiracetam will be increased from 500mg/day on week 2 and this dose will be slowly titrated to a total of 3000mg/day or maximum tolerated dose (MTD). Subjects will remain on their full dosage through week 13.
At the end of week 13, participants will undergo detoxification from methadone over a 4-week period (weeks 13-17) and discontinuation from levetiracetam over a concurrent 2-week period.
All participants will receive weekly 1-hour of individual psychotherapy (Cognitive Behavioral Treatment) with experienced clinicians specifically trained to deliver the therapy and who will receive ongoing supervision. The primary outcomes will be reduction in cocaine use, as assessed by self-report and thrice-weekly urinalyses. Secondary outcomes will include weeks in treatment (retention), reported medication side effects (medication tolerability), and change in measures of: cocaine craving, anxiety symptoms and opiate withdrawal symptoms. This study will occur at the Outpatient Treatment Research Program in Building 36 at the VA CT Healthcare System.
- Conditions
- Cocaine Dependence, Opioid Dependency
- Being tested
- levetiracetam, Placebo
- Keywords
- GABAergic, levetiracetam
- Medical subject headings
- Cocaine-Related Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
levetiracetamDrug
The participants will start receiving Levetiracetam 500mg in the mornings of the first day on week 2. The dose will be titrated every third day, until the target dose of 3000mg/day is achieved by week 4. The study medication must be titrated to 3000 mg/day or to the subject's maximum tolerated dose (MTD). The physician overseeing this titration as well as all study staff will be blind to the subject's medication administration. The medication will be discontinued over a two-week period.
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Levetiracetam tablets Receives: Drug: levetiracetam |
| 2 | Placebo comparator | matching placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change of Thrice Weekly Cocaine Free Urine Toxicology From Week 1 to 13
The primary outcome variable was the change from baseline to week 13 of the thrice weekly cocaine-free urine scores. In this repeated ordinal variable, 0 represented all 3 urine samples submitted by the subject as positives, 1 represented some urine samples submitted by the subject were negative, and 2 represented all 3 urine samples submitted by the subjects were negative for cocaine. Balancing the distribution between these categories improved the models for the analysis of repeated ordinal data. Data is summarized as number of participant that were cocaine free urine (score 2) per week by group.
Measured: Weekly from baseline to week 12
Secondary outcomes (3)
Change of Thrice Weekly Opioid Free Urine Toxicology From Week 1 to 13
The secondary outcome variable was the change from baseline to week 13 of the thrice weekly opioid-free urine scores. In this repeated ordinal variable, 0 represented all 3 urines samples submitted by the subject as positives, 1 represented some urine samples submitted by the subject were negative, and 2 represented all 3 urines samples submitted by the subjects were negative for opioids excluding methadone. Balancing the distribution between these categories improved the models for the analysis of repeated ordinal data. Data summarized by number of participants who were had opioid free urine samples (score 2) per week by group.
Measured: Weekly from baseline to week 12
Treatment Retention
Weekly from week 1 to 13
Measured: Week 13
Cocaine Craving
Weekly cocaine craving was measure at intake and weekly after with the Visual Analog Scale (VAS) of the Cocaine Selective Severity Assessment. The VAS measures the intensity of cocaine craving with a scale from 0 (No desire at all) to 7 (Unable to resist), and frequency of cocaine craving in the previous 24 hours with a scale from 0 ( never) to 7 ( all the time). The scale is totaled for a maximum number of 14, the minimum is 0. (Kampman et al., 1998; Mulvaney et al., 1999).
Measured: Weekly from baseline to week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2007 (estimated)
- Study startJul 2007
- Primary completionJun 2008
- Study completionOct 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Cocaine DependenceStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Responsible party
- Sponsor
- Investigators
- Gerardo Gonzalez, MD, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00577005
- Sponsor's protocol ID
- 0707002832
- Other IDs
- 5R01DA017782-04, NIDA-5R01DA017782-04, Yale-0508000534, VA-gg0006
- Acronym
- Keppra-DB
- Status last verified
- Jan 2018
- First submitted
- 17 Dec 2007
- Last updated
- 17 Jan 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 17 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Levetiracetam (Keppra) Treatment for Cocaine Dependence in Methadone-Maintained Patients
- ClinicalTrials.gov ID
- NCT00577005
- Acronym / sponsor ID
- Keppra-DB / 0707002832
- Conditions
- Cocaine Dependence, Opioid Dependency
- Keywords
- GABAergic, levetiracetam
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Study start
- Jul 2007
- Primary completion
- Jun 2008 (actual)
- Study completion
- Oct 2008 (actual)
- First posted
- 19 Dec 2007 (estimated)
- Results
- Posted 24 Apr 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Concurrent dependence on cocaine occurs in up to 50% of the over one million opiate dependent patients in spite of methadone maintenance treatment being highly effective for opiate dependence and having excellent treatment retention. Cocaine dependence has remained largely unresponsive to medications both in and outside of these methadone programs. We have initial data from our open-label study with levetiracetam showing that this medication is well tolerated and may reduce cocaine use in this cocaine-abusing methadone treated population.
The specific aim of this study is to evaluate the efficacy of levetiracetam 3 grams/day in modifying cocaine-using behavior, reducing cocaine craving and attenuating cocaine's reinforcing effect among methadone-maintained patients. The primary outcomes will be reduction in cocaine use as assessed by self-report and thrice-weekly urinalyses. Secondary outcomes will include weeks in treatment (retention) and change in measures of cocaine craving, anxiety symptoms and opiate withdrawal symptoms.
Detailed description
This 17-week double-blind, placebo controlled randomized pilot clinical trial will provide treatment for 40 cocaine-dependent opioid dependent patients. Participants, aged 18-65 years, will be randomized to receive levetiracetam 3000 mg/day or placebo while concurrently receiving treatment with methadone. Baseline cocaine use will be determined during the first week of treatment participation. (Gossop et al., 1997) The study design will have three overlapping phases that are summarized below: 1) A one week methadone fixed induction (week 1) and flexible methadone stabilization phase (weeks 2-13); 2) an 12-week "treatment" phase (weeks 2-13), consisting of slow titration and stabilization on study medication; and 3) a four week "taper, detoxification or transfer" phase (weeks 13-17).
During the first week of induction onto methadone, participants will be administered increasing doses of methadone starting at 30 mg daily and increased up to 60 mg daily by the end of the first week. This methadone dose will be adjusted for stabilization of opiate withdrawal symptoms using a flexible dosing from 40 mg up to 150 mg between weeks 2 to 12. This range has been found to be adequate for the vast majority of patients receiving methadone in our program and is designed to accommodate participants who may not be able to tolerate the higher maintenance doses or may still experience withdrawal symptoms, respectively. We may increase or decrease this amount on a case-by-case basis based on physician assessment of self-reported and observed symptoms.
Starting on week 2 subjects will start study medication in one of two randomly assigned experimental groups: levetiracetam 3000 mg /day (active medication) or placebo (inactive medication). Concurrent with the stabilization on methadone, levetiracetam will be increased from 500mg/day on week 2 and this dose will be slowly titrated to a total of 3000mg/day or maximum tolerated dose (MTD). Subjects will remain on their full dosage through week 13.
At the end of week 13, participants will undergo detoxification from methadone over a 4-week period (weeks 13-17) and discontinuation from levetiracetam over a concurrent 2-week period.
All participants will receive weekly 1-hour of individual psychotherapy (Cognitive Behavioral Treatment) with experienced clinicians specifically trained to deliver the therapy and who will receive ongoing supervision. The primary outcomes will be reduction in cocaine use, as assessed by self-report and thrice-weekly urinalyses. Secondary outcomes will include weeks in treatment (retention), reported medication side effects (medication tolerability), and change in measures of: cocaine craving, anxiety symptoms and opiate withdrawal symptoms. This study will occur at the Outpatient Treatment Research Program in Building 36 at the VA CT Healthcare System.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: levetiracetamLevetiracetam tablets |
| 2 | Placebo comparator | Drug: Placebomatching placebo |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Between the ages of 18-65 years.
- Participants must demonstrate current opioid dependence as determined by study physician or APRN, self-reported history of opioid dependence for one year and a positive urine of opiates. Participants may be transferred from other methadone maintenance programs, including the WHVA methadone program.
- Participants also must be current users of cocaine with self-reported use of cocaine > 1 time/week in at least one month preceding study entry, cocaine-positive urine screen and score over 3 as assessed with the Severity Dependence Scale.
- Women of childbearing age are eligible to be included in the study if they have a negative pregnancy test at screening, agree to adequate contraception to prevent pregnancy, to have monthly pregnancy tests, and they understand the risk of fetal toxicity due to medication and cocaine.
Key exclusion criteria (5 listed)
- Current diagnosis of other drug or alcohol dependence (other than opiates, cocaine or tobacco).
- Patients with serious medical illness (e.g., major cardiovascular, renal, endocrine, hepatic, and serious neurological disorders including any history of seizures).
- Patients with current serious psychiatric illness or history of psychosis, schizophrenia, bipolar type I disorder and subjects with suicidal or homicidal thoughts or taking psychotropic medications.
- Women who are pregnant, nursing or refuse to use a reliable form of birth control or refuse monthly testing.
- Screening liver function tests (SGOT or SGPT) greater than 3 times normal and renal function test (creatinine) greater than 1.5 mg/dl.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| levetiracetamThe participants will start receiving Levetiracetam 500mg in the mornings of the first day on week 2. The dose will be titrated every third day, until the target dose of 3000mg/day is achieved by week 4. The study medication must be titrated to 3000 mg/day or to the subject's maximum tolerated dose (MTD). The physician overseeing this titration as well as all study staff will be blind to the subject's medication administration. The medication will be discontinued over a two-week period. | Drug | 1 |
| Placebo | Drug | 2 |
Primary outcome
Change of Thrice Weekly Cocaine Free Urine Toxicology From Week 1 to 13
Time frame: Weekly from baseline to week 12
The primary outcome variable was the change from baseline to week 13 of the thrice weekly cocaine-free urine scores. In this repeated ordinal variable, 0 represented all 3 urine samples submitted by the subject as positives, 1 represented some urine samples submitted by the subject were negative, and 2 represented all 3 urine samples submitted by the subjects were negative for cocaine. Balancing the distribution between these categories improved the models for the analysis of repeated ordinal data. Data is summarized as number of participant that were cocaine free urine (score 2) per week by group.
3 secondary outcomes
Change of Thrice Weekly Opioid Free Urine Toxicology From Week 1 to 13
Time frame: Weekly from baseline to week 12
Treatment Retention
Time frame: Week 13
Cocaine Craving
Time frame: Weekly from baseline to week 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jan 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gerardo Gonzalez, MD principal investigator
Yale University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing levetiracetam in people with Cocaine Dependence and Opioid Dependency, run by Yale University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Apr 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change of Thrice Weekly Cocaine Free Urine Toxicology From Week 1 to 13 (time frame: Weekly from baseline to week 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jan 2018.